Research published in JCI elucidates role of DSCR-1s induced in endothelial cells due to VEGF.
Researchers have determined that the short form of the protein DSCR-1 (DSCR-1s) dampens the immune response to inflammation in mice. While the existence of DSCR-1s in the cells that line blood vessels was previously shown, until now its role was not fully understood, according to the scientists.
These findings appear in The Journal of Clinical Investigation in a paper called “The Down syndrome critical region gene 1 short variant promoters direct vascular bedspecific gene expression during inflammation in mice.” The team included scientists from the University of Tokyo and Harvard Medical School.
Past research showed that VEGF induces DSCR-1s expression in endothelial cells, which in turn negatively feeds back to attenuate endothelial cell activation. In the current study, the investigators set out to characterize the role of the promoter that drives DSCR-1s expression in mediating inducible expression in vivo and to determine the functional relevance of DSCR-1s in inflammation.
They report that expression of DSCR-1s was induced in vivo in mouse endothelial cells in a number of different inflammatory settings including after administration of LPS, a bacterial component, and transplantation with a tumor xenograft. Further they found that following administration of LPS, DSCR-1deficient mice displayed increased mortality rates, while DSCR-1overexpressing mice were protected. These results establish a protective role for this protein in controlling the host response to infection, the researchers note.